Elucidation the mechanism of epithelial differentiation induced by claudin, tight junction protein.

• Project/Area Number: 26460475
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Fukushima Medical University
• Principal Investigator: Tomikawa Naoki 福島県立医科大学, 医学部, 講師 (80468587)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 上皮分化 / 幹細胞 / 細胞間接着分子 / 細胞間接着 / 核内受容体 / シグナル分子同定 / ノックアウト細胞株 / リコンビナントタンパク作製 / シグナル分子

Outline of Final Research Achievements

In this study, we clarified that claudin-6, cell-cell adhesion protein, induces the differentiation from stem cells to epithelial cells using mouse embryonic stem cell line and mouse embryonic stem cells. Moreover, we identified the mechanism that claudin-6 activated Src and Blk, a intracellular signaling molecule by directly interaction and subsequently activated PI3K、Akt and mToR. Claudin-6-induced signaling cascade arrived in retinoid receptor, a nuclear receptor, and regulate the expression of the epithelial differentiation-related molecules.

Research Products

• [Journal Article] Liver X receptor reduces proliferation of human oral cancer cells by promoting cholesterol efflux via up-regulation of ABCA1 expression. (2015)
  • Author(s): Kaneko T*, Kanno C*, Ichikawa-Tomikawa N*, Kashiwagi K, Yaginuma N, Ohkoshi C, Tanaka M, Sugino T, Imura T, Hasegawa H, Chiba H.
  • Journal Title: Oncotarget Volume: 6 Pages: 33345-57
  • Peer Reviewed / Open Access
• [Journal Article] Co-expression of S100A14 and S100A16 correlates with a poor prognosis in human breast cancer and promotes cancer cell invasion. (2015)
  • Author(s): Tanaka M, Ichikawa-Tomikawa N, Shishito N, Nishiura K, Miura T, Hozumi A, Chiba H, Yoshida S, Ohtake T, Sugino T
  • Journal Title: BMC Cancer Volume: 184
  • Peer Reviewed
• [Journal Article] Laminin α1 regulates age-related mesangial cell proliferation and mesangial matrix accumulation through the TGFβ pathway (2014)
  • Author(s): Ning L, Kurihara H, Vega S, Ichikawa-Tomikawa N, Xu Z, Nonaka R, Kazuno S, Yamada Y, Miner JH, Arikawa-Hirasawa E
  • Journal Title: Am J Pathol Volume: 184 Pages: 1683-94
  • Peer Reviewed
• [Presentation] Cldn6による上皮分化誘導シグナルの全貌解明 (2016)
  • Author(s): 冨川直樹
  • Organizer: 第６８回日本細胞生物学会
  • Place of Presentation: 京都
  • Year and Date: 2016-06-15
• [Presentation] 幹細胞の上皮分化誘導機構における、核内受容体およびプロテインキナーゼの機能解析 (2016)
  • Author(s): 柏木維人
  • Organizer: 第１０５回日本病理学会
  • Place of Presentation: 仙台
  • Year and Date: 2016-05-12
  • Int'l Joint Research
• [Presentation] クローディン－６の上皮分化誘導シグナルには、SrcとBlkが機能している。 (2015)
  • Author(s): 冨川直樹、柏木維人、杉本幸太郎、千葉英樹
  • Organizer: 第104回日本病理学会大会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-04-30
  • Int'l Joint Research
• [Presentation] クローディン－６/Srcファミリーキナーゼシグナルは幹細胞の上皮分化を誘導する (2014)
  • Author(s): 冨川直樹
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] 細胞間接着シグナルとク核内受容体のクロストークによる幹細胞の新規上皮分化機構 (2014)
  • Author(s): 冨川直樹
  • Organizer: 第66回日本細胞生物学会大会
  • Place of Presentation: 奈良
  • Year and Date: 2014-06-11 – 2014-06-13
• [Presentation] クローディン－６による上皮分化誘導シグナルに関与するsrc family kinase分子の同定 (2014)
  • Author(s): 冨川直樹
  • Organizer: 第103回日本病理学会大会
  • Place of Presentation: 広島
  • Year and Date: 2014-04-24 – 2014-04-26
• [Remarks] 福島県立医科大学基礎病理学講座
  • URL: http://www.fmu.ac.jp/home/p2/index.html
• [Remarks] 講座ホームページ
  • URL: http://www.fmu.ac.jp/home/p2/